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Tissue distribution and concentration gradients of macro- and micro-elements in the papilla, medulla, and cortex of human kidney with renal calculi were measured with spectrometer. An uninvolved portion of the hypernephroma kidney was used as control. Cadmium (Cd), cobalt (Co), and molybdenum (Mo) were least in amount in renal papilla as compared with the cortex and medulla in renal stone kidney. Overall there was less Mo in stone kidney tissue, and also significantly less when compared with that of control renal papilla. Considering the reported fact that Mo was found in high concentrations in urinary tract stones and our data that Mo was less in stone kidney, it is speculated that Mo may play some unexplained but significant role in certain stage(s) of the stone formation.

We attempted to produce a malignant urinary bladder carcinoma in mice by transplanting MBT-2 cells. MBT-2 carcinoma about 3.0 x 10(3) cells/0.02 ml were successfully transplanted into the bladder wall with an incidence of 80% (20/25) after three experimental weeks. Inoculated tumor cells grew expansively into the bladder cavity from the bladder submucosa, and invaded the muscle layer. We observed that tumors caused gross hematuria and bilateral hydronephrosis. This malignant tumor model in which a tumor is implanted into its original organs seems to be useful for predicting clinical effectiveness in experimental cancer therapy.

Cross-linking of effector T cells to target cancer cells augments their tumor lytic activities. Here we describe a new method of conjugating lymphokine-activated killer (LAK) cells with cancer-specific monoclonal antibody. The LAK cells were biotinylated, treated with avidin, and conjugated with biotinylated monoclonal antibody. These monoclonal antibody-conjugated LAK cells showed specifically enhanced killing activities against anti-tumor antibody-reactive cancer cells, and cold target cells specifically inhibited their activities.

196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 0.01) from 0.60 +/- 0.89 to 0.084 +/- 0.305 times/patient. year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux. Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR.

Fifty-five female C3H/He mice were given 0.05% N-bytyl-N-(4-hydroxybutyl) nitrosamine in their drinking water for 18 weeks. In week 19, eleven mice (group 3) were sacrificed to confirm that they all had bladder carcinoma. The remaining mice were divided into two groups. Group 1 received 20 Gy of proton irradiation over the whole pelvis, while group 2 received no treatment as a control. After 3 weeks all the animals were sacrificed and their bladders were resected to weigh and to examine histologically. The average weight of the bladder, as an index of the tumor volume, was 67.7 mg in group 1, 120.6 mg in group 2 and 106.5 mg in group 3. There was a significant differences (p less than 0.05) between group 1 and group 2. The incidences of superficial (pT1) and deeply invasive (pT2-3) bladder carcinomas were [10/18 (56%) and 8/18 (39%)] in group 1, [3/17 (18%) and 14/17 (82%)] in group 2 and [2/11 (18%) and 9/11 (82%)] in group 3, respectively. These rates of incidence were significantly different (p less than 0.05) between group 1 and group 2. However, there was no significant difference (p = 0.068) between group 1 and group 3. These results indicate that proton irradiation is effective for treatment of invasive bladder carcinoma in mice.

The sonic detection and recording systems of urethral sounds generated during micturition were developed. This procedure was tentatively postulated as "urophonography" and its recording diagram as a "urophonogram". Classification of urophonograms was done on the basis of analyzing normal healthy male volunteers and patients with benign prostatic hyperplasia. Four types of urophonograms were demonstrated according to the shape and characteristics. Types 1, 2, 3 and 4 were characterized by a diamond shape, irregular occurrences of sound spikes, the mixture of Types 1 and 2 and no remarkable sound spikes respectively. Types 1, 2, and 3 were found in BPH, while Type 4 was demonstrated in normal healthy male volunteers. After prostatectomy a high percentage of Type 4 was demonstrated. The frequency (Hz) of these sounds was around 650. Diamond shape sound showed higher value of power gain (dB) than irregular type sound. The wave length was around 0.50 (m). Comparison of urophonographic studies with conventional uroflowmetric investigation was undertaken. Urophonography was useful for investigations of dysfunctional voiding and lower urinary tract obstruction.

A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.

Clinicopathological studies were made on 105 patients with renal cell carcinoma who visited us from January 1978 to August 1989. The results were as follows: 1. Overall 3, 5 and 10-year survival rates were 60.4%, 49.8% and 44.5%, respectively. 2. Patients in Robson stage I survived longer than those in stage III, and patients in stage II survived longer than those in stage IV with a significant difference. 3. A significant difference did not exist between patients in stages lower than pT2 and those in pT3a, while patients in pT3a survived longer than those in stages higher than pT3b. 4. Patients with grade 1 tumors survived longer than those with grade 2 tumors, and patients with grade 2 tumors survived longer than those with grade 3 tumors with a significant difference. 5. Patients with clear cell subtype survived longer than those with granular cell subtype and mixed subtype with a significant difference, while a significant difference did not exist between patients with granular cell subtype and those with mixed subtype. 6. Patients with INF alpha tumors survived longer than those with INF beta tumors with a significant difference. There was the same significant difference in patients with grade 2 tumors.

Fourteen patients (age range 50-79 mean 64.2) with locally advanced bladder cancer or CIS have been treated with combination of selective intra-arterial infusion of adriamycin (ADM) and/or cisplatin (CDDP) and local hyperthermia, prior to planed surgical resection. The follow-up periods ranged from 33 to 70 months (median 52). Clinical staging was based on biopsy, CT, Echo, chest X-ray, bone scintigraphy, and IVP. The initial tumor stage was Tis in 1 patients, cT2 in 4, and cT3 in 9. Catheterization technique: with the patient in the prone position, the gluteal muscles were dissected to expose the inferior gluteal artery, then catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week, more than eight times during hyperthermia. The total dose of ADM and CDDP were 40-360 mg and 50-360 mg. Local bladder hyperthermia was achieved with a radiofrequency generator. Novatherm IH-500 (Inter-Nova Co. Ltd, Japan). Intravesical temperature was maintained over 40 degrees C for an hour. Surgical resection included total cystectomy (10 patients), partial cystectomy (3) and TUR (1). Of evaluable 8 patients, CR was obtained in 2 patients, PR in 4, NC in 1 and PD in 1. The survival rate (Kaplan Meier method) at 3 years was 71.4% (n = 9) and at 5 years, 62.5% (n = 4). Five patients died, but two of them died of other causes (traffic accident and spinal cord injury). Severe toxicity, consisting of bone marrow suppression (3) perineal erosion (3) and ischialgia (1), was well tolerated. In conclusion, our result suggests combination therapy of intra-arterial chemotherapy and local hyperthermia is safe with minimal systemic side effects, and may prolong survival with invasive bladder cancer.

A new bisphosphonate, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) assessing their effects on tumor induced osteolysis using human prostate adenocarcinoma cells in nude mice. The method consisted of inoculating transplantable human prostate cancer cells subcutaneously over the calvaria in nude mice resulting in a local tumor causing fragmentation of the bone. The parameters included assessing the extent of decreased osteolysis in bone as judged by X-ray and histological examination. The results showed the following sequence of potency: AHBuBP greater than AHPrBP greater than HEBP. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumor. This inhibition was obtained with no apparent effect on the growth of the tumor. AHBuBP appears to be an interesting new bisphosphonate for future clinical use.

Urodynamic approach to the disorders of the urinary tract has been based on the knowledge of anatomy and neurophysiology of this abnormality. The development of this field included uroflowmetry, cystometry, urethral profilometry, and electromyogram of the external sphincter. In addition to these investigations new trends in urodynamic field were reviewed. With the advent of muscle biochemistry intra-renal urodynamics has been advocated. These researches would be expected to clarify the mechanism of intra-renal reflux. The another investigation was urophonography. When the urine passed through the posterior urethra the urethral sound occurred. The detecting, recording and analyzing systems were developed. This method would be entirely a new method of urodynamic study.

A new experimental method to test the effect of drugs on tumor induced osteolysis using a transplantable bladder tumor (MBT-2) in mice has been designed. The method consists of inoculating tumor cells sc over the calvaria in mice, causing in a local tumor with fragmentation of the bone. This was accompanied by adjacent osteoblastic changes, which were evaluated by X-ray and histological examination. APD, a bisphosphonate derivative, at a dose of 3 mg/kg to 10 mg/kg sc protected the bone by decreasing the extent of osteolysis as judged by the same criteria. This inhibition was obtained without apparent effect on the growth of the bladder tumor in mice.

Renal biopsies were performed on 25 patients with reflux nephropathy to clarify the relationship between the pathological findings and clinical parameters. Biopsy specimens were obtained at anti-reflux operation by open renal biopsy. Glomerular lesions were classified as focal, diffuse, segmental and global sclerosis. Tubulo-interstitial changes were defined according to the principle advocated by Cotran and expressed as the percentage of the lesions. The clinical parameters consisted of the grades of VUR, the grades of renal scarring, renal function and the daily urinary protein excretion. A significant relationship was noted between the grades of VUR and those of renal scarring. The percentage of global sclerosis in the kidney revealed a close relationship with the grades of VUR and the percentage of tubulo-interstitial changes but not with the renal function or the daily urinary protein excretion. Focal segmental hyalinosis and/or sclerosis (FSHS) lesions were presented in 3 of 25 cases (12%). The pathological findings of the FSHS lesions had a close relationship with the renal function and the daily urinary protein excretion and the prognosis of the kidney. The other patients without FSHS lesions displayed an unchanged renal function. Based on these observations, it is clear that the prognosis of the patients with vesico-ureteral reflux could be predicted from the histopathological findings; the presence of FSHS lesions suggests a poor prognosis for the kidney. The degree of daily proteinuria represents a useful parameter for evaluating the progression of the reflux nephropathy.

In order to evaluate the nephrotoxicity by antibiotics, effects of these agents were investigated in terms of protein synthesis and nucleic acid metabolism in the kidneys of Wistar rats. Aminoglycoside antibiotics (streptomycin, kanamycin, gentamycin), tetracycline (doxytetracycline), chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used. These antibiotics were given to the rats for 5 successive days. On the 6th day 14C-6-orotic acid and 14C-1-leucine were administered intraperitoneally. Incorporation rates of these tracers into ribonucleic acid and protein fraction in rat kidney ribosomes (polysomes) were measured. Another experiment was undertaken in vitro by separating the polysome fraction from the rat kidneys. In vitro acellular protein synthesis using these polysomes was established. Effects of antibiotics on the incorporation rates of 14C-1-leucine were examined. Marked reduction of incorporation of these tracers into nucleic acid and protein in vivo and in vitro was induced by aminoglycoside antibiotics. These facts suggest that aminoglycoside antibiotics develop nephrotoxicity by interfering with the metabolism of ribosomal RNA and protein.

We report 31 cases of renal cell carcinoma treated with interferon. Indicators defined as bidimensionally measurable mass were present in 20 cases, which included 19 cases with metastatic lesions and one case with primary site who did not receive nephrectomy. Treatment were performed with interferon-gamma in 9 cases, and with interferon-alpha in 14 cases. Of them, 3 cases received alpha-interferon following gamma-interferon treatment. Remained 11 cases had no evidence of disease after radical nephrectomy or surgical removal of metastatic lesions, and received interferon-alpha as post operative adjuvant therapy. In 18 evaluable cases, one case (6%) showed minor response; 8 cases (44%) no change and 9 cases (50%) progressive disease. Survival rates (Kaplan-Meier's method) of minor response and no change cases at 1, 2 years were 89%, 59%. Those of progressive disease cases were 22% and 11%, respectively. Of 11 cases received post operative adjuvant therapy, recurrence was observed in four cases (36%) with the mean follow up period of 11 months. Frequent side effects were fever (62%), leukocytopenia (56%) anorexia (38%), fatigue (26%). Efficacy of interferon to metastatic renal cell carcinoma in this study is limited. Further studies are required to determine the benefit of post operative adjuvant therapy with interferon.

Between February, 1984, and June, 1988, 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy was performed on 48 patients with suspected pheochromocytoma at our hospital. Whole body image and/or spot images were obtained 24, 48 and 72 hours after injection of 0.5 mCi of 131I-MIBG. In 10 of 12 patients with surgically proven pheochromocytoma, 131I-MIBG was accumulated in the primary and metastatic tumor. 131I-MIBG scintigraphy was negative in 2 patients. One case of renal cyst had the accumulation of 131I-MIBG but the disease could be confirmed. By 131I-MIBG scintigraphy sensitivity was 83% (10/12), and specificity was 97% (35/36). Heart intensity was much higher in patients with nonpheochromocytoma than those with pheochromocytoma. Thus 131I-MIBG scintigraphy proved to be safe, non-invasive and specific in the diagnosis of pheochromocytoma.

Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assessed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was successful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.

In order to assess the potential nephrotoxicity of antibiotics, effects of these agents on rat kidney lysosomal membrane were investigated in various conditions. Antibiotics were given to Wistar rats for 5 successive days. After nephrectomy rat lysosomes were separated and their membrane stability was examined by measuring the activities of acid-phosphatase. In addition, after separation of lysosomes from normal untreated Wistar rats, antibiotics were added in the incubation system to assess the in vitro effect of antibiotics. Effects of renal ischemia and the lysosomal membrane stabilizer (cortisol) were also examined. Aminoglycosides antibiotics (streptomycin, kanamycin, gentamycin), doxytetracycline, chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used for this purpose. It was clearly pointed out that aminoglycosides interfered with the lysosomal stability in vivo and in vitro. After a 60 minutes ischemia of the rat kidneys by clamping the renal arteries, effects of antibiotics on administration of 5 successive days on rat lysosomal stability were investigated. It was demonstrated that aminoglycosides also made the lysosomal membrane more unstable. Effects of the lysosomal stabilizer, cortisol, on rat kidney lysosomes were examined. Use of cortisol simultaneously with an antibiotic was more effective than that before and after it.

Reported is a case of 67-year-old man with a recurrent gastric carcinoma that was associated with a possible lymphatic metastasis to the scrotum. Seven years earlier (October, 1980), since an adenocarcinoma of the stomach was present, a subtotal gastrectomy was performed. At that time, a IIc-like advanced tumor with a ul-III, measuring 32 x 28 mm in size, was noted on the anterior wall of the corpus near the greater curvature of the stomach, on macroscopical examination of the resected specimen. Microscopic findings showed a poorly differentiated adenocarcinoma with an involvement of the serosa but without a lymph node metastasis (H0, P0, n0, se, stage III). In July 1987, a tumor in the right scrotum was found and the patient underwent surgery. The resected specimen revealed a histologically cancerous involvement of the testis, the epididymis, the tunica vaginalis testis, and the spermatic cord. The cancerous cells showed the same poorly differentiated adenocarcinoma which had been observed in the primary locus of the stomach. Judging from these findings, this case was diagnosed as a recurrent gastric carcinoma with a lymphatic metastasis to the scrotum.

To establish a new indicator for the classification of human urinary bladder cancers, the nucleoli of normal epithelial and neoplastic cells were analyzed, using morphometric techniques. By electron microscopy, the nucleolar profiles of cells from grade 2 and 3 transitional cell carcinomas were often small and irregular. Morphometry showed that the nucleolar volumes, nucleolar/nuclear volume ratios, volume densities of various nucleolar components, and the numbers of fibrillar centers (FCs) altered significantly with an increase in tumor grade. In particular, an increase in FC numbers in the nuclei of higher grade tumors was associated with a decrease in individual volume. The number of FCs in intact urothelial cells obtained from patients with bladder tumors is significantly larger than in the normal urothelial cells. This may be related to the multicentric origin of bladder cancers. These results suggest that morphometric analysis of nucleoli is useful in evaluating the degree of differentiation and invasive capacity of human bladder tumor cells. In particular, the number and individual volume of FCs may be an indicator of tumor malignancy.

We report a case of nonseminomatous testicular tumor with lymph node involvement and multiple lung and liver metastases. The patient was considered to have a poor prognosis. He received systemic chemotherapy and cytoreductive surgery. Postoperatively a residual metastatic tumor in the liver was treated by intrahepatic arterial cisplatinum-diaminedichloride infusion. Follow-up observation has revealed no evidence of recurrence for 30 months since the last treatment.

The effectiveness of a preoperative combination of chemotherapy and irradiation on advanced bladder cancer was evaluated. The combination therapy group (Arm I) included 21 patients, the preoperative chemotherapy group (Arm II) 14 patients, and a group without preoperative treatment, 35 patients. There were no distinguishing background factors among the three groups. Chemotherapy included vincristine, adriamycin, mitomycin, bleomycin/and 5-FU. A total of 3000 rads was irradiated locally, and the results were promising. The Arm I group was superior to the other two groups in terms of response rate, histological effectiveness and downstaging effects. Also, the 5-year-survival rate for Arm I was much better than in the other groups. There were no great differences in adverse effects between Arm I and II.

A new epithelial cell line, TSU-Pr1, from a human prostatic adenocarcinoma metastatic to lymph node has been established in long term tissue culture. The cultured cells show loss of contact inhibition, rapid growth in vitro and growth in athymic nude mice. Karyotypic analysis demonstrated an aneuploid karyotype with a modal chromosome number of 80 including a Y-chromosome and at least 10 marker chromosomes. The cells produced only a small amount of prostatic acid phosphatase, and heterotransplanted tumors did not have nuclear androgen receptors.

Pedal lymphangiography was done on 21 patients with carcinoma of the prostate. The lymphangiograms were positive in 11 cases and negative in 10. Out of 9 patients who underwent lymphadenectomy (5 with positive and 4 with negative findings), operative findings were in agreement with the lymphangiogram in 8 patients (89%). Lymphangiography should be used as the primary procedure in all cases where aggressive therapy is being considered.

Chemotherapy of advanced bladder cancer aims to destroy all the cancer cells in the host. For this purpose the most suitable and effective anticancer agents should be chosen. There have been many methods to select the anti-cancer drugs: sensitivity test. However, no reliable tests are available. We developed new anti-cancer sensitivity test, using the radio-active nucleic acids precursors; C14-Formate and C14-Adenine. This test revealed that Cisplatin, Adriamycin, and Mitomycin C were the most potent for the transitional cell carcinoma of the urinary bladder. Chemotherapy with a single agent was disappointing. Combined use of these agents was rather promising. Among them combination of cis-platin with Adriamycin and/or cyclophosphamide was the most effective. However, the overall response rate was reported around 50%. Multi-disciplinary treatment including surgery, irradiation, chemotherapy, and immunotherapy was disclosed to be useful for the treatment of bladder cancer. Since 1977 25 cases were treated with this mode of therapy in our clinic. Anti-tumor effect was remarkable. The categories, disappeared, and over 50% decrease of the mass, were found in 96% of the patients. Also, down-staging was demonstrated in 20% of the cases. Histologically no cancer cells were found in the surgical specimens of 3 cases and no viable cancer cells in 3 cases respectively. From these results it is now assumed that multi-disciplinary treatment is promising for the treatment of bladder cancer.

Several postoperative adjuvant therapeutic modalities have been adopted in attempts to reduce the recurrence rate of superficial bladder cancer. However, no definite conclusions on the effectiveness of intravesical chemoprophylaxis have been reached. A randomized clinical study on intravesical chemoprophylaxis was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the recurrence rates among 575 patients with superficial transitional cell carcinoma of the urinary bladder. Group A received 30 mg/30 ml Adriamycin; group B received 20 mg/40 ml Adriamycin; group C received 20 mg/40 ml mitomycin C, and group D, no treatment (for control). Instillation was performed twice a week for 4 weeks after surgery. The postoperative observation period was 18 months. The overall recurrence rate in group D was 61.5%, which was statistically higher than in the other groups. The Adriamycin and Mitomycin C groups showed recurrence rates of 43%-48% and 57%, respectively. Intravesical Adriamycin and Mitomycin C appeared to be effective in the prophylaxis of recurrence during this observation period. The main side-effect was cystitis syndrome, which was observed in 10%-20% of the patients. There were no life-threatening adverse effects in this series of patients.

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Sera from 23 patients with renal cell carcinoma were tested for circulating immune complexes by Clq binding assay and immunosuppressive acidic protein by single radial immunodiffusion. The mean values of circulating immune complexes and immunosuppressive acidic protein in the patients were significantly higher than those of normal controls, and over-all positive rates were 52 and 35 per cent, respectively. There was a significant correlation between immunosuppressive acidic protein levels and the extent of tumor invasion. Immunosuppressive acidic protein may be a more useful marker than circulating immune complexes. However, presently synthetic evaluations of patients with various nonspecific markers, including these 2 factors, will be necessary.

The incidence of prostatic cancer has been reported to be low in Japan and Asia, compared with the USA and European countries. However, it is now on the increase in Japan. The possible etiological factors for the origin and development of prostatic cancer were examined on 187 patients with this malignancy who visited the Department of Urology, University of Tokyo during the past 16 years. No evidence that these factors were specifically related to prostatic cancer, was found. The possible etiology and differences in incidence between Japan, the USA, and European countries are discussed.

Recently we have developed an entirely new method of sonic detection of lower urinary tract disorders during micturition. This procedure was designated as "urophonography" and its recording as "urophonogram". Sixteen patients with prostatic cancer before and three months after anti-androgenic therapy and ten healthy male volunteers underwent urophonography. The urophonograms were classified into four types. Type 1 was characterized by its diamond shape, while Type 2 was characterized by its random sound spikes. Type 3 was a mixture of Types 1 and 2. Type 4 had few sound spikes. Analysis of these urophonograms also revealed that the frequencies of these urethral sounds belonged to the range from 0.4 to 1.5 KHz. The amplitude (power) of the sounds was in the range of 40-60 dB. Healthy volunteers belonged to Type 4. Prostatic cancer patients belonged to Types 1, 2 and 3 at 18.8, 68.8, nad 12.4%, respectively. After the treatment the percentages of Types 1, 2, 3, and 4 changed to 18.8, 50.0, 0, and 31.2%, respectively. Comparison of uroflowmetric parameters with urophonograms showed that Type 2 patients showed a lesser degree of micturition disturbances, evidenced by these parameters. It was considered that urophonograms were useful as urodynamic investigation.

A cooperative study of UFT was conducted in cases of far-advanced renal cell carcinoma. UFT was administered daily at a dose of 300-600 mg FT equivalent for at least 4 weeks. Forty-one patients were entered into the protocol from the 19 collaborating institutions in the group. The antitumor effects of the drug were clinically evaluable in 25 patients according to the response criteria proposed by the Koyama-Saito study group. Seven were not eligible and 9 were cases of protocol violation. Complete response (CR) and partial response (PR) were observed in 2 and 5 patients, respectively, showing a response rate of 28.0%. One patient showed minor response, 8 stable disease and 9 progressive disease. It took about 22 weeks and 16 weeks to attain CR and PR, respectively. Lung metastasis was the lesion showing most the favorable response to this treatment. Twenty-eight patients were used for evaluating the adverse effects of the drug. Gastrointestinal symptoms such as nausea, vomiting and anorexia, were observed most frequently, while bone marrow suppression was minimal. Only three patients had to be taken off the drug due to its adverse effects. In conclusion, UFT was considered to be one of the most effective drugs for the treatment of far-advanced renal cell carcinoma.

A 77 year-old woman presented with the chief complaint of a mass in the right upper quadrant. The examination on admission including IVP, echography, Ga scintigraphy, barium enema, CT scan, and angiography revealed that the right kidney and ascending colon were displaced by the mass. Under the diagnosis of retroperitoneal tumor, operation was carried out. Most of the mass was resected with the right kidney. The pathological diagnosis of the resected tumor revealed well differentiated liposarcoma. Convalescence was uneventful and the patient has been well and free from disease for 14 months. Based on our experience and the review of the pertinent literature in English and Japanese, we emphasize the importance of definite surgery and close follow up, as liposarcoma is frequently recurrent.

A phase I study of a recombinant gamma interferon (S-6810) was conducted in a cooperative study involving 11 institutions. S-6810 was administered at doses of 2, 4, 8, 12, 32 and 64 X 10(6) U/m2 by one-hour infusion for 5 consecutive days. A total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills occurred in about 80% of patients. The incidences of other toxicities were fatigue in 50%, gastrointestinal toxicities in 30-40%, and changes in hepatic enzymes and hematologic toxicities in 20-30%. Dose-limiting factors were judged to be hypotension, leukopenia and central nervous toxicity. Maximum tolerated dose was 64 X 10(6) U/m2 and an optimal dose for phase II study was considered to be 6 X 10(6) U/m2 by daily chronic schedule. Blood concentration was highest at the end of infusion, and then decreased rapidly with a biphasic curve. The peak concentrations were elevated by escalation of doses. A partial response was observed in a patient with mycosis fungoides.

Long-term administration of PSK was made in 40 patients with urological cancer. Mean duration of the administration was 201, 358 and 243 days for the patients with bladder cancer, renal cancer and other urological cancers, respectively. The clinical evaluations were performed by the standard of Japan Society for Cancer Therapy and historical control study. In some cases, it seemed that the immunological therapy by PSK was a benefit to some degree. However, more accurate evaluation should be made by the matched control study.

Renal cell carcinoma is the third most frequent cause of urological cancer death in Japan. The first is bladder cancer and the second is prostatic cancer. However, there has been no clinical trial of mass screening for early detection of renal cell carcinoma. With a view to discovering a method of early detection for renal cell carcinoma, we analyzed the procedures for discovering renal cell carcinoma in 33 patients who were treated at our hospital. In 10 patients, carcinoma had been discovered accidentally without gross hematuria, abdominal mass or flank pain. Seven of these patients were first suspected of having renal cell carcinoma by ultrasonography, two by intravenous pyelography (IVP) and one by computed tomography. Seven out of nine patients operated on were surgically diagnosed as having stage I and two as having stage II. Ultrasonography is far better than IVP from the points of view of noninvasiveness, ease of performance and accuracy. In our study, ultrasonography was the most useful method for early detection of renal cell carcinoma. However, for the mass screening of renal cell cancer by ultrasonography, it is necessary to make its specificity and sensitivity clear and to debate its cost effectiveness.